Postdoctoral Fellow for the Colorectal Cancer Lab (ref. PD/24/03)
We are seeking a Postdoctoral Researcher to participate in the research network MACH3CANCER (https://mach3cancer.org/) aiming to apply high-throughput 3D live imaging technology to explore questions related to tumor cell plasticity and drug resistance.
This international consortium has developed cutting-edge microscopy tools that contribute to the understanding of how cancer cells behave in complex 3D structures and enable robust interrogation of responses to cancer therapy with single cell resolution. Screens will include longitudinal live cell imaging assays and use sophisticated phenotypic endpoints - with the potential to link to and inform subsequent single cell genomic and proteomic analysis.
New, modular, open source, high content analysis (HCA) instrumentation and software tools are currently being developed to address the imaging challenges associated with 3D cell cultures and organoids. In particular, an Oblique Plane Microscope (OPM) for live-cell High-content. Analysis of patient-derived organoids upon lightsheet illumination has already been implemented at IRB Barcelona, based on the most recent prototype developed by the inventors of OPM at Imperial College (see dOPM by Sparks et al: https://doi.org/10.1364/BOE.409781), and it is a central resource to the project, in combination with other high-throughput screening resources (e.g. the NIKON LIPSI HTS confocal microscope). Altogether, this will lead to enhanced understanding of the mechanisms of drug resistance and more effective high content screens for new therapies.
This project is financed by CRUK-AECC (GEACC19006BAT; from the Accelerator Awards of the "Fundación de la Asociación Española contra el Cancer (FAECC)").
The selected candidate will work at the Batlle Lab and the Advanced Digital Microscopy (ADM) Core Facility.
The Batlle Lab is an internationally recognized laboratory that explores the connection between stem cells and cancer and the mechanisms of immune evasion utilized by metastatic colorectal cancers. For more information, please check: https://www.irbbarcelona.org/ebatlle.
Advanced Digital Microscopy (ADM) Core Facility at IRB Barcelona is a first class bioimaging platform offering a full range of optical technologies, commercial or custom, e.g. confocal, multiphoton, spinning-disk, super-resolution, high-content, lightsheet, nanosurgery or FLIM modalities. ADM actively develops technology in lightsheet imaging, tissue clearing, large datasets analysis, and has coordinated the NEUBIAS network (2016-2021). ADM technologies are accessible to local, national and international scientists, in particular through Eurobioimaging-ERIC (participation in two Spanish Nodes: Mesoscopic Imaging and Live & Intravital Imaging). https://adm.irbbarcelona.org/
KEY PUBLICATIONS RELATED TO THE PROJECT:
Cañellas-Socias, et al and Batlle E. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells. Nature. Nov;611(7936):603-613. 2022.
Alvarez-Varela, et al. and Batlle E. Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy. Nature Cancer. Sep;3(9):1052-1070. 2022.
Herpes et al. and Batlle E, Throsby M. Functional screening on patient-derived organoids identifies a therapeutic bispecific antibody that triggers EGFR degradation in LGR5+ tumor cells. Nature Cancer. 3: 418-436. 2022.
Morral et al. and Batlle E. Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer. Cell Stem Cell. 26: 845-861. 2020
Cortina C, et al. and Batlle E. A genome editing approach to study cancer stem cells in human tumors. EMBO Molecular Medicine. 9 (7): 869-879. 2017
Tosi S, Bardia L, Filgueira MJ, Calon A and Colombelli J. LOBSTER: An environment to design bioimage analysis workflows for large and complex fluorescence microscopy data. Bioinformatics. 36(8):2634–2635. 2020
Conduct independent research in the area of advanced microscopy applied to research with organoids, including novel spinning-disk and lightsheet-based high-throughput instruments.
Standardize advanced microscopy workflows for organoids screening across four European facilities.
Develop and/or use complex bioimage analysis assays for single cell analysis in high-content live large 3D image datasets.
EXPERIENCE, KNOWLEDGE, SKILLS:
Applications are invited from highly motivated and ambitious researchers with a PhD degree.
The applicant is expected to have experience in the area of microscopy.
Applicants should have excellent interpersonal and communication skills, organizational skills to plan experimental bench-work and the ability to work both as part of the team as well as independently.